Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter October 10, 2016

Biophysical methods toolbox to study ABC exporter structure and function

  • Thomas Marcellino and Vasundara Srinivasan EMAIL logo
From the journal Biological Chemistry

Abstract

ABC exporters are highly dynamic membrane proteins that span a huge spectrum of different conformations. A detailed integrated approach of cellular, biochemical and biophysical characterization of these ‘open’, ‘closed’ and other intermediate states is central to understanding their function. Almost 40 years after the discovery of the first ABC transporter, thanks to the enormous development in methodologies, a picture is slowly emerging to visualize how these fascinating molecules transport their substrates. This mini review summarizes some of the biophysical tools that have made a major impact in understanding the function of the ABC exporters.

Award Identifier / Grant number: GZ:SR 113/1-1

Funding statement: We gratefully acknowledge the generous financial support of the Deutsche Forschungsgemeinschaft (DFG Research Grant) (Grant/Award Number: ‘GZ:SR 113/1-1’) and the LOEWE program of the State of Hesse.

Acknowledgements

We gratefully acknowledge the generous financial support of the Deutsche Forschungsgemeinschaft (DFG Research Grant) (Grant/Award Number: ‘GZ:SR 113/1-1’) and the LOEWE program of the State of Hesse.

References

Borbat, P.P., Surendhran, K., Bortolus, M., Zou, P., Freed, J.H., and McHaourab, H.S. (2007). Conformational motion of the ABC transporter MsbA induced by ATP hydrolysis. PLoS Biol. 5, e271.10.1371/journal.pbio.0050271Search in Google Scholar

Choudhury, H. G., Tong, Z., Mathavan, I., Li, Y., Iwata, S., Zirah, S., Rebuffat, S., van Veen, H.W., and Beis, K. (2014). Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state. Proc. Natl. Acad. Sci. USA 111, 9145–9150.10.1073/pnas.1320506111Search in Google Scholar

Dawson, R.J. and Locher, K.P. (2006). Structure of a bacterial multidrug ABC transporter. Nature 443, 180–185.10.1038/nature05155Search in Google Scholar

Hellmich, U.A. and Glaubitz, C. (2009). NMR and EPR studies of membrane transporters. Biol. Chem. 390, 815–834.10.1515/BC.2009.084Search in Google Scholar

Herget, M., Baldauf, C., Scholz, C., Parcej, D., Wiesmuller, K.H., Tampe, R., Abele, R., and Bordignon, E. (2011). Conformation of peptides bound to the transporter associated with antigen processing (TAP). Proc. Natl. Acad. Sci. USA 108, 1349–1354.10.1073/pnas.1012355108Search in Google Scholar

Higgins, C.F. and Linton, K.J. (2004). The ATP switch model for ABC transporters. Nat. Struct. Mol. Biol. 11, 918–926.10.1038/nsmb836Search in Google Scholar

Hohl, M., Briand, C., Grutter, M.G., and Seeger, M.A. (2012). Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation. Nat. Struct. Mol. Biol. 19, 395–402.10.1038/nsmb.2267Search in Google Scholar

Hohl, M., Hurlimann, L.M., Bohm, S., Schoppe, J., Grutter, M.G., Bordignon, E., and Seeger, M.A. (2014). Structural basis for allosteric cross-talk between the asymmetric nucleotide binding sites of a heterodimeric ABC exporter. Proc. Natl. Acad. Sci. USA 111, 11025–11030.10.1073/pnas.1400485111Search in Google Scholar

Jones, P.M. and George, A.M. (2014). A reciprocating twin-channel model for ABC transporters. Q Rev. Biophys. 47, 189–220.10.1017/S0033583514000031Search in Google Scholar

Kaur, H., Lakatos, A., Spadaccini, R., Vogel, R., Hoffmann, C., Becker-Baldus, J., Ouari, O., Tordo, P., McHaourab, H., and Glaubitz, C. (2015). The ABC exporter MsbA probed by solid state NMR – challenges and opportunities. Biol. Chem. 396, 1135–1149.10.1515/hsz-2015-0119Search in Google Scholar

Kim, J., Wu, S., Tomasiak, T.M., Mergel, C., Winter, M.B., Stiller, S.B., Robles-Colmanares, Y., Stroud, R.M., Tampe, R., Craik, C.S., et al. (2015). Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter. Nature 517, 396–400.10.1038/nature13872Search in Google Scholar

Kodan, A., Yamaguchi, T., Nakatsu, T., Sakiyama, K., Hipolito, C.J., Fujiok, A., Hirokane, R., Ikeguchi, K., Watanabe, B., Hiratake, J., et al. (2014). Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog. Proc. Natl. Acad. Sci. USA 111, 4049–405410.1073/pnas.1321562111Search in Google Scholar

Kunert, B., Gardiennet, C., Lacabanne, D., Calles-Garcia, D., Falson, P., Jault, J.M., Meier, B.H., Penin, F., and Bockmann, F. (2014). Efficient and stable reconstitution of the ABC transporter BmrA for solid-state NMR studies. Front. Mol. Biosci. 1, 5.10.3389/fmolb.2014.00005Search in Google Scholar

Lange, V., Becker-Baldus, J., Kunert, B., van Rossum, B.J., Casagrande, F., Engel, A., Roske, Y., Scheffel, F.M., Schneider, E., and Oschkinat, H. (2010). A MAS NMR study of the bacterial ABC transporter ArtMP. Chembiochem 11, 547–555.10.1002/cbic.200900472Search in Google Scholar

Lee, J.-Y., Kinch, L.N., Borek, D.M., Wang, J., Wang, J., Urbatsch, I.L., Xie, X.-S., Grishin, N.V., Cohen, J.C., Otwinowski, Z., et al. (2016). Crystal structure of the human sterol transporter ABCG5/ABCG8. Nature 533, 561–564.10.1038/nature17666Search in Google Scholar

Lee, J. Y., Yang, J.G., Zhitnitsky, D., Lewinson, O., and Rees, D.C. (2014). Structural basis for heavy metal detoxification by an Atm1-type ABC exporter. Science 343, 1133–1136.10.1126/science.1246489Search in Google Scholar

Li, J., Jaimes, K.F., and Aller, S.G. (2014). Refined structures of mouse P-glycoprotein. Protein Sci. 23, 34–46.10.1002/pro.2387Search in Google Scholar

Liu, W., Wacker, D., Wang, C., Abola, E., and Cherezov, V. (2014). Femtosecond crystallography of membrane proteins in the lipidic cubic phase. Philo.s Trans. R Soc. Lond. B Biol. Sci. 369, 20130314.10.1098/rstb.2013.0314Search in Google Scholar

Marcoux, J., Wang, S.C., Politis, A., Reading, E., Ma, J., Biggin, P.C., Zhou, M., Tao, H., Zhang, Q., Chang, G., et al. (2013). Mass spectrometry reveals synergistic effects of nucleotides, lipids, and drugs binding to a multidrug resistance efflux pump. Proc. Natl. Acad. Sci. USA 110, 9704–9709.10.1073/pnas.1303888110Search in Google Scholar

Mehmood, S., Domene, C., Forest, E., and Jault, J.M. (2012). Dynamics of a bacterial multidrug ABC transporter in the inward- and outward-facing conformations. Proc. Natl. Acad. Sci. USA 109, 10832–10836.10.1073/pnas.1204067109Search in Google Scholar

Moeller, A., Lee, S.C., Tao, H., Speir, J.A., Chang, G., Urbatsch, I.L., Potter, C.S., Carragher, B., and Zhang, Q. (2015). Distinct conformational spectrum of homologous multidrug ABC transporters. Structure 23, 450–460.10.1016/j.str.2014.12.013Search in Google Scholar

Neutze, R., Branden, G., and Schertler, G.F. (2015). Membrane protein structural biology using X-ray free electron lasers. Curr. Opin. Struct. Biol. 33: 115–125.10.1016/j.sbi.2015.08.006Search in Google Scholar

Oldham, M.L., Hite, R.K., Steffen, A.M., Damko, E., Li, Z., Walz, T., and Chen, J. (2016). A mechanism of viral immune evasion revealed by cryo-EM analysis of the TAP transporter. Nature 529, 537–540.10.1038/nature16506Search in Google Scholar

Popot, J. L. (2010). Amphipols, nanodiscs, and fluorinated surfactants: three nonconventional approaches to studying membrane proteins in aqueous solutions. Annu. Rev. Biochem. 79: 737–775.10.1146/annurev.biochem.052208.114057Search in Google Scholar

Rees, D.C., Johnson, E., and Lewinson, O. (2009). ABC transporters: the power to change. Nat. Rev. Mol. Cell Biol. 10, 218–227.10.1038/nrm2646Search in Google Scholar

Rodriguez, J.A., Ivanova, M.I., Sawaya, M.R., Cascio, D., Reyes, F.E., Shi, D., Sangwan, S., Guenther, E.L., Johnson, L.M., Zhang, M., et al. (2015). Structure of the toxic core of alpha-synuclein from invisible crystals. Nature 525, 486–490.10.1038/nature15368Search in Google Scholar

Rosenberg, M.F., Callaghan, R., Ford, R.C. and Higgins, C.F. (1997). Structure of the multidrug resistance P-glycoprotein to 2.5 nm resolution determined by electron microscopy and image analysis. J. Biol. Chem. 272, 10685–10694.10.1074/jbc.272.16.10685Search in Google Scholar

Shintre, C.A., Pike, A.C., Li, Q., Kim, J.I., Barr, A.J., Goubin, S., Shrestha, L., Yang, J., Berridge, G., Ross, J., et al. (2013). Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states. Proc. Natl. Acad. Sci. USA 110, 9710–9715.10.1073/pnas.1217042110Search in Google Scholar

Srinivasan, V., Pierik, A.J., and Lill, R. (2014). Crystal structures of nucleotide-free and glutathione-bound mitochondrial ABC transporter Atm1. Science 343, 1137–1140.10.1126/science.1246729Search in Google Scholar

Tang, M., Sperling, L.J., Berthold, D.A., Schwieters, C.D., Nesbitt, A.E., Nieuwkoop, A.J., Gennis, R.B., and Rienstra, C.M. (2011). High-resolution membrane protein structure by joint calculations with solid-state NMR and X-ray experimental data. J. Biomol. NMR 51, 227–233.10.1007/s10858-011-9565-6Search in Google Scholar

Ward, A., Reyes, C.L., Yu, J., Roth, C.B., and Chang, G. (2007). Flexibility in the ABC transporter MsbA: Alternating access with a twist. Proc. Natl. Acad. Sci. USA 104, 19005–19010.10.1073/pnas.0709388104Search in Google Scholar

Wilkens, S. (2015). Structure and mechanism of ABC transporters. F1000Prime Rep. 7, 14.10.12703/P7-14Search in Google Scholar

Received: 2016-6-30
Accepted: 2016-10-5
Published Online: 2016-10-10
Published in Print: 2017-2-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 24.3.2023 from https://www.degruyter.com/document/doi/10.1515/hsz-2016-0244/html
Scroll Up Arrow